Abnormal synaptic pruning during adolescence underlying the development of psychotic disorders
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PURPOSE OF REVIEW: Excessive synaptic pruning has first been suggested by Irwin Feinberg (1982) as an important pillar in the pathophysiology in schizophrenia (SCZ). This article reviews recent developments highlighting factors implicated in aberrant synaptic pruning and its contribution to disease onset and emergence of cognitive symptoms in SCZ. Unraveling these factors provides new insights for potential prevention and treatment strategies for psychotic disorders. RECENT FINDINGS: Increased pruning in SCZ was recently confirmed by a positron emission tomography-study employing the novel tracer [11C]UCB-J, demonstrating the consequential loss of synaptic density. Recent evidence supports the contributing role of astrocytes and increased complement-mediated microglial pruning in disease onset and cognitive symptoms in SCZ. Increased microglial pruning is mediated specifically by C4. Furthermore, environmental factors (e.g., infections and stress) can lead to dysbiosis which was recently linked to microglial activation and pruning in SCZ. SUMMARY: Recent findings render the pruning machinery a potential target for early treatment and prevention in individuals at high risk for SCZ. Minocycline can improve cognition in SCZ, probably by reducing excessive pruning. Probiotics might also have beneficial effects on cognition, although recent findings are not encouraging. N-acetyl-cysteine recovers functional connectivity in SCZ both in vitro and in vivo, making it an interesting candidate.
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Positron emission tomography studies have shown increased synaptic density in sensory cortices and decreased synaptic density in superior frontal areas in people at risk for psychotic symptoms.
“positron emission tomography studies have shown increased synaptic density in sensory cortices and decreased synaptic density in superior frontal areas in people at risk for psychotic symptoms.”
From Towards an Integrative Account of Potential Mechanisms Mediating the Path From Sleep Dysfunction to Hallucinations (2025) · cites this paper as [96]
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Imaging Synaptic Density: The Next Holy Grail of Neuroscience?
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Self-citation
- Authors
- Germann, M., Brederoo, S. G., & Sommer, I. E. C.
- Affiliations
- University Medical Center Groningen (NL)
- Venue
- Current Opinion in Psychiatry
- Published
- 2021-02-03
- Volume
- 34
- Issue
- 3
- Pages
- 222-227
- ISSN
- 0951-7367 (ISSN-L)
- 1473-6578
- PMC
- PMC8048735
- OpenAlex
- W3128655558
- Cited by
- 102
- References
- 51
- Citations by year
- 2026: 16 · 2025: 16 · 2024: 33 · 2023: 17 · 2022: 14 · 2021: 6
- FWCI
- 3.13
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Current Opinion in Psychiatry (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion, cc-by-nc-nd)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion, cc-by-nc-nd)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- synaptic pruning, schizophrenia, adolescence, psychosis, complement C4, astrocytes, synaptic density, cognitive symptoms, dysbiosis, infection, stress, minocycline, probiotics, N-acetylcysteine, functional connectivity, disease onset
- MeSH terms
- Adolescent, Cognition, Humans, Neuronal Plasticity, Psychotic Disorders, Schizophrenia, Microglia
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